Résumé
INTRODUCCIÓN: Helicobacter pylori afecta a más de 50% de la población mundial, siendo más prevalente en poblaciones de nivel socioeconómico bajo; esta bacteria constituye la principal causa de cáncer gástrico a nivel global. OBJETIVO: Determinar la frecuencia y los factores asociados a la infección por H. pylori en personas adultas que viven en el centro histórico de la ciudad de Cajamarca, en el norte del Perú. MATERIAL Y MÉTODO: Estudio descriptivo que incluyó 124 personas encuestadas mediante un cuestionario y evaluadas mediante endoscopía y cultivo de biopsia gástrica. Una biopsia por persona fue sometida a prueba de ureasa y los cultivos se confirmaron por reacción de polimerasa en cadena (RPC). RESULTADOS: La frecuencia de infección fue de 60,5 % (IC 95% 51,3 - 69,2). El análisis univariado demostró asociación significativa entre la infección y la edad (p = 0,002), y entre la infección y el antecedente de patología gástrica (p = 0,015). El análisis multivariado reveló dos factores asociados: edad (OR = 0,94; IC95% 0,90-0,97) y antecedente de infección por H. pylori (OR = 0,23; IC95% 0,08 - 0,67). CONCLUSIONES: Existe alta frecuencia de infección por H. pylori en esta población; la edad y el antecedente de infección constituyen factores asociados que deben evaluarse con mayor profundidad.
BACKGROUND: Helicobacter pylori affects more than 50% of the world's population, being more prevalent in populations of low socioeconomic status. H. pylori is the main cause of gastric cancer globally. AIM: To establish the frequency and factors associated with H. pylori infection in adults living in the historic center of Cajamarca City, in northern Peru. METHODS: This was a descriptive study that included 124 individuals surveyed through a questionnaire and evaluated through endoscopy and gastric biopsy culture. One biopsy per person underwent the urease test, and the cultures were confirmed by PCR. RESULTS: The frequency of infection was 60.5% (95% CI 51.3 - 69.2). In the univariate analysis, there was a significant association between the infection and age (p = 0.002), and between the infection and a history of gastric pathology (p = 0.015). The multivariate analysis revealed two associated factors: age (OR = 0.94; 95% CI 0.90 - 0.97), and history of H. pylori infection (OR = 0.23; 95% CI 0.08 - 0.67). CONCLUSIONS: There is a high frequency of H. pylori infection in this population, and the age and history of H. pylori infection are factors that should be further evaluated.
Sujets)
Humains , Mâle , Femelle , Adulte d'âge moyen , Infections à Helicobacter/diagnostic , Infections à Helicobacter/épidémiologie , Pérou/épidémiologie , Urease/analyse , Biopsie , Réaction de polymérisation en chaîne , Études transversales , Analyse multifactorielle , Enquêtes et questionnaires , Facteurs de risque , Endoscopie gastrointestinale , Helicobacter pylori/isolement et purification , Helicobacter pylori/génétique , Infections à Helicobacter/microbiologie , Muqueuse gastrique/microbiologie , Muqueuse gastrique/anatomopathologieRésumé
SUMMARY: Overexpression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in various tumor tissues and cell lines was found to promote tumor cell proliferation, migration, and invasion. However, the role of MALAT1 in gastric cancer (GC) is still unclear. We aimed to investigate the correlation between long-chain non-coding RNAs (lncRNAs), MALAT1, MicroRNAs (miRNA) and vascular endothelial growth factor A (VEGFA) in gastric cancer and to disclose underlying mechanism. The correlation between MALAT1 levels and clinical features was analyzed by bioinformatics data and human samples. The expression of MALAT1 was down regulated in AGS cells to detect the cell proliferation, migration, and invasion characteristics, as well as the effects on signal pathways. Furthermore, we validated the role of MALAT1/miR-330-3p axis in GC by dual luciferase reporter gene assays. Expression of MALAT1 was higher in cancer tissues than in para-cancerous tissues. The high MALAT1 level predicted malignancy and worse prognosis. Down-regulation of MALAT1 expression in AGS cells inhibited cell proliferation, migration, and invasion by targeting VEGFA. By dual luciferase reporter gene assay and miR-330-3p inhibitor treatment, we demonstrate that MALAT1 sponged miR-330-3p in GC, leading to VEGFA upregulation and activation of the mTOR signaling pathway. The MALAT1/miR-330-3p axis regulates VEGFA through the mTOR signaling pathway and promotes the growth and metastasis of gastric cancer.
Se descubrió que la sobreexpresión del transcrito 1 de adenocarcinoma de pulmón asociado a metástasis (MALAT1) en varios tejidos tumorales y líneas celulares promueve la proliferación, migración e invasión de células tumorales. Sin embargo, el papel de MALAT1 en el cáncer gástrico (CG) aún no está claro. Nuestro objetivo fue investigar la correlación entre los ARN no codificantes de cadena larga (lncRNA), MALAT1, los microARN (miARN) y el factor de crecimiento endotelial vascular A (VEGFA) en el cáncer gástrico y revelar el mecanismo subyacente. La correlación entre los niveles de MALAT1 y las características clínicas se analizó mediante datos bioinformáticos y muestras humanas. La expresión de MALAT1 se reguló negativamente en las células AGS para detectar las características de proliferación, migración e invasión celular, así como los efectos sobre las vías de señales. Además, validamos el papel del eje MALAT1/miR- 330-3p en GC mediante ensayos de genes indicadores de luciferasa dual. La expresión de MALAT1 fue mayor en tejidos cancerosos que en tejidos paracancerosos. El alto nivel de MALAT1 predijo malignidad y peor pronóstico. La regulación negativa de la expresión de MALAT1 en células AGS inhibió la proliferación, migración e invasión celular al apuntar a VEGFA. Mediante un ensayo de gen indicador de luciferasa dual y un tratamiento con inhibidor de miR-330-3p, demostramos que MALAT1 esponjaba miR-330-3p en GC, lo que lleva a la regulación positiva de VEGFA y la activación de la vía de señalización mTOR. El eje MALAT1/miR-330-3p regula VEGFA a través de la vía de señalización mTOR y promueve el crecimiento y la metástasis del cáncer gástrico.
Sujets)
Humains , Tumeurs de l'estomac/génétique , Tumeurs de l'estomac/anatomopathologie , Facteur de croissance endothéliale vasculaire de type A , Sérine-thréonine kinases TOR , ARN long non codant , ARN/génétique , Transduction du signal , Régulation de l'expression des gènes tumoraux , Mouvement cellulaire , Technique de Western , Apoptose , Gènes rapporteurs , Prolifération cellulaire , Réaction de polymérisation en chaine en temps réel , Invasion tumoraleRésumé
RESUMEN Antecedentes: el cáncer gástrico (CG) representa un problema de salud pública en Colombia y el mundo. Dado que la mayoría de los pacientes se encuentran en estadios avanzados en el momento del diagnóstico. desarrollar estrategias de manejo. como la terapia de conversión (TC). es una necesidad cada vez mayor en su tratamiento. Objetivo: estimar los resultados con la TC en el tratamiento de pacientes con CG avanzado en el Instituto Nacional de Cancerología de Colombia (INC). Material y métodos: serie de casos de pacientes con adenocarcinoma gástrico incurable llevados a quimioterapia de inducción y cirugía con intención curativa. entre los años 2010 y 2021. Se revisaron de forma retrospectiva los datos clínico-patológicos y de supervivencia. La supervivencia global (SG) se calculó desde la fecha de la primera quimioterapia hasta la muerte. Las funciones de supervivencia se estimaron con tablas de vida y por el método de Kaplan-Meier y se realizaron curvas de supervivencia a 3 y 5 años. Resultados: se analizaron los datos de 23 pacientes con edad promedio de 56 años. 17 (74%) fueron varones. El criterio de irresecabilidad más frecuente fue un tumor T4b en 13 casos (56.5%). Todos recibieron TC. La mediana de seguimiento fue de 28 meses. Se documentaron 11 recurrencias (52%). La mediana de supervivencia fue de 41.2 meses y la SG a 3 y 5 años de 57.7% y 38.5%. respectivamente. Conclusiones: la TC permitió obtener una SG aceptable de pacientes seleccionados con CG avanzado incurable. Esta estrategia requiere una cuidadosa selección y manejo multidisciplinario en centros oncológicos de referencia.
ABSTRACT Background: Gastric cancer (GC) represents a public health problem in Colombia and worldwide. Since most patients are at advanced stages at the time of diagnosis. it is necessary to develop management strategies as conversion therapy (CT). Objective: The aim of this study was to estimate the results of CT for treating patients with advanced and GC at Instituto Nacional de Cancerología de Colombia (INC). Material and methods: We included patients with incurable gastric cancer who underwent induction chemotherapy and intended curative surgery between 2010 and 2021. The clinical and pathological data and survival of the patients included were retrospectively reviewed. Overall survival (OS) was calculated from the time of initiation of chemotherapy until the date of death. Survival functions were estimated using the life table and Kaplan-Meier methods. and survival curves at 3 and 5 years were constructed. Results: 23 patients were analyzed; mean age was 56 years. and 17 (74%) were men. The most common criterion indicating unresectability was a T4b tumor in 13 cases (56.5%). All the patients underwent CT. Median follow-up was 28 months. Eleven patients developed disease recurrence (52%). Median survival was 41.2 months. and 3- and 5-year OS was 57.7% and 38.5%. respectively. Conclusions: CT provided an acceptable OS rate for selected patients with incurable advanced GC. This strategy requires an adequate selection of patients and multidisciplinary management in reference oncology centers.
Résumé
El cáncer gástrico (CG), es la primera causa de muerte por cáncer, en hombres, y la tercera en mujeres, en Chile. No obstante ello, el CG bifocal (CGB) es una situación poco frecuente. El objetivo de este manuscrito fue reportar un caso de CGB, con linfonodos negativos en un paciente con cirrosis hepática, que fue intervenido quirúrgicamente; y revisar la evidencia existente respecto de sus características morfológicas, terapéuticas y pronósticas. Caso clínico: Hombre de 74 años diabético, hipertenso, insuficiente cardíaco y cirrótico; portador de CGB (subcardial y antro-pilórico), diagnosticado por endoscopia y con confirmación histológica de ambas lesiones; operado en Clínica RedSalud Mayor Temuco en septiembre de 2023. En el intraoperatorio se verificó además la coexistencia de una lesión de aspecto metastásico en el segmento III del hígado, y adhesión de la región antro-pilórica a la vesícula biliar. Se realizó gastrectomía total, linfadenectomía D2, esófago-yeyuno anastomosis término-lateral, resección segmentaria hepática (segmento III) y colecistectomía. El paciente permaneció 6 días en la UCI debido a que desarrolló insuficiencia hepática (encefalopatía leve y ascitis). Se alimentó vía enteral por sonda naso-yeyunal. Posteriormente inició alimentación oral progresiva, la que fue bien tolerada. Completó 11 días de hospitalización en servicio médico-quirúrgico, donde mejoró actividad neurológica, hasta su alta domiciliaria. Actualmente, lleva dos meses desde su operación, se encuentra en buenas condiciones generales, y el Comité Oncológico decidió no dar quimioterapia adyuvante. Se presenta un caso inusual de CG de tipo bifocal, respecto de lo cual hay escasa información disponible. Se logró realizar cirugía con intención curativa en un paciente de alto riesgo, con un resultado exitoso.
SUMMARY: Gastric cancer (GC) is the first cause of death from cancer in men, and the third one in women, in Chile. However, a bifocal GC (BGC) is uncommon. The aim of this study was to report a case of CGB, with negative-lymph nodes in a patient with liver cirrhosis, who underwent surgery; and review the existing evidence regarding its morphological, therapeutic and prognostic characteristics. Clinical case: A 74-year-old male patient with a medical history of diabetes, hypertension, congestive heart failure, and cirrhosis underwent surgical intervention for GC located in subcardial and antro- pyloric regions. The diagnosis was established via endoscopy and confirmed histologically. Surgery was performed at the RedSalud Mayor Temuco Clinic in September 2023. During intraoperative assessment, the coexistence of a lesion with metastatic-like characteristics in segment III of the liver was also verified, along with adhesions between the antro-pyloric region and the gallbladder. Surgical approach encompassed total gastrectomy, D2 lymphadenectomy, esophago-jejunostomy, segmental hepatic resection, and cholecystectomy. Subsequently, the patient required a six-day stay in ICU due to the development of hepatic insufficiency, characterized by mild encephalopathy and ascites. Enteral nutrition was administered via a naso-jejunal tube, followed by a gradual transition to oral feeding, which was well-tolerated. The patient completed an 11-day hospitalization period in the medical-surgical ward, during which his neurological function improved significantly, resulting in his discharge. At present, 2 months post-surgery, the patient remains in satisfactory general health, and the Oncology Committee decided not to proceed with adjuvant chemotherapy. This case represents a rare instance of bifocal GC, for which there is limited available literature. Surgical intervention with curative intent was successfully carried out in a high-risk patient, yielding a positive outcome.
Sujets)
Humains , Mâle , Sujet âgé , Tumeurs de l'estomac/chirurgie , Tumeurs de l'estomac/anatomopathologie , Tumeurs primitives multiples , GastrectomieRésumé
ABSTRACT Background: Adriamycin (ADM) resistance remains an obstacle to gastric cancer chemotherapy treatment. Objective: The objective of this study was to study the role and mechanism of transcription factor E2F7 in sensitivity to ADM chemotherapeutic agents in gastric cancer. Methods: Cell viability and cell sensitivity were assessed by CCK-8 and IC50 values of ADM were calculated. The impact of ADM on cellular proliferative capacity was assessed through colony formation assay. The binding relationship between E2F7 and PKMYT1 was then verified by dual luciferase assay and chromatin immunoprecipitation assay. ERK1/ERK2 and p-ERK1/p-ERK2 protein expression levels were detected by western blot. Results: In both gastric cancer tissue and ADM-resistant cells, a conspicuous upregulation of E2F7 and PKMYT1 was observed. Upregulated PKMYT1 was notably enriched in the MAPK signaling pathway. Enhanced levels of E2F7 were shown to not only drive gastric cancer cell proliferation but also engender a reduction in the sensitivity of these cells to ADM. Furthermore, PKMYT1 emerged as a downstream target of E2F7. Activation of E2F7 culminated in the transcriptional upregulation of PKMYT1, and silencing E2F7 reversed the inhibitory impact of PKMYT1 overexpression on ADM sensitivity in gastric cancer cells. Conclusion: E2F7/PKMYT1 axis might promote the proliferation and partially inhibit ADM sensitivity of gastric cancer cells by activating the MAPK pathway.
Résumé
RESUMEN Latinoamérica presenta una alta prevalencia de infección por Helicobacter pylori (Hp). Entre 1996-2003 la prevalencia en Santiago de Chile fue del 70%; estudios recientes presentan una disminución en esta infección. Actualizar la frecuencia de Hp es fundamental debido a su impacto en la salud asociado. Objetivo: Nuestro objetivo fue describir la tendencia de la infección por Hp en pacientes que asisten a endoscopía digestiva alta (EDA) ambulatoria en una población chilena. Materiales y métodos: Se realizó un estudio observacional retrospectivo de pacientes mayores de 18 años que asistieron a una primera EDA con test rápido de ureasa entre 2010-2020. La tendencia en el tiempo fue descrita mediante análisis de series de tiempo. Se construyó un modelo Poisson para estimar el riesgo de infección, ajustado por edad y sexo. Resultados: Se incluyeron 11 355 pacientes [66,9% mujeres; edad media 52 años; Hp 41,6%]. El sexo masculino presentó una mayor frecuencia de infección por Hp [RR 1,13; (IC95%:1,08-1,18)]. La frecuencia de Hp disminuyó significativamente desde 45,1% en 2010 hasta 29% en 2020, con 36% menor probabilidad de presentar infección por Hp en 2020 con respecto al 2010 [RR 0,64; (IC95%:0,55-0,74)]. Se proyectó un descenso progresivo en la tendencia de infección por Hp hasta valores cercanos al 25% para el año 2025. Conclusión: Se observó una reducción significativa en la infección por Hp entre los años 2010-2020. Esta disminución pudiese ser explicada mediante la incorporación de políticas públicas de salud en la última década asociadas a cambios sociosanitarios.
ABSTRACT Latin America presents a high prevalence of Helicobacter pylori (Hp) infection. Between 1996-2003, the prevalence in Santiago, Chile, was 70%; recent studies indicate a decrease in this infection. Updating the frequency of Hp is crucial due to its associated health impact. Objective: Our objective was to describe the trend in Hp infection in patients undergoing ambulatory esophagogastroduodenoscopy (EGD) in a Chilean population. Materials and methods: A retrospective observational study was conducted on patients over 18 years old who attended a first EGD with a rapid urease test between 2010-2020. Time trends were described through time series analysis. A Poisson model was constructed to estimate the risk of infection, adjusted for age and gender. Results: 11,355 patients were included [66.9% females; mean age 52 years; Hp 41.6%]. Male gender presented a higher frequency of Hp infection [RR 1.13; (95% CI: 1.08-1.18)]. Hp frequency infection decreased significantly from 45.1% in 2010 to 29% in 2020, with a 36% lower probability of Hp infection in 2020 compared to 2010 [RR 0.64; (95% CI: 0.55-0.74)]. A progressive decline in Hp infection trend was projected, reaching values close to 25% by year 2025. Conclusion: A significant reduction in Hp infection was observed between 2010-2020. This decrease could be explained by the implementation of public health policies in the last decade associated with socio-sanitary changes.
Résumé
Gastric cancer （GC） is one of the most common cancers in the world， with hidden symptoms， complex pathogenesis， high morbidity， high mortality， and poor prognosis. As one of the classical apoptosis pathways， mitochondrial apoptosis has been widely described in the apoptosis escape by GC cells. Mitochondrial apoptosis can regulate the proliferation， invasion， and metastasis of GC cells via oxidative stress， cell cycle， mitochondrial membrane potential， mitochondrial translocation and other mechanisms， and it is one of the potential targets of traditional Chinese medicine （TCM） intervention to restore the mitochondrial function in GC. The theory of spleen-mitochondria in correlation explains that spleen deficiency and cancer toxin are the root causes of mitochondrial apoptosis. Accordingly， the TCM treatment should follow the basic principle of invigorating spleen to restore healthy Qi and removing cancer toxin to eliminate the root cause. Mitochondrial apoptosis can be promoted by inhibiting oxidative stress， promoting cell cycle arrest， and reducing mitochondrial membrane potential. This therapy can improve the energy metabolism， restore the mitochondrial structure and function， and prevent the occurrence and development of GC， with mild side effects and low drug resistance. However， the mechanism of mitochondrial apoptosis in GC and the target of TCM intervention in GC have not been systematically reviewed. Therefore， this paper systematically summarized the effects of mitochondrial apoptosis on the occurrence and development of GC and the role of TCM in the treatment of GC by intervening in mitochondrial apoptosis， aiming to provide a theoretical reference for the treatment and further research of GC.
Résumé
Objective To explore the significance of the combined strategy of oncolytic virus infection, immune effector cell supplement, and immune checkpoint blocking in the treatment of gastric cancer. Methods A tumor-bearing nude mouse model of gastric cancer was treated with recombinant oncolytic vaccinia virus carrying the CXCL9 gene of T lymphocyte chemokine and IL-7gene (VV-IL7-CXCL9) obtained in previous experiments. We established a triple-intervention group of recombinant oncolytic vaccinia virus intratumoral injection+cytotoxic T lymphocyte (CTL)+immune checkpoint blocker (PD-1 monoclonal antibody), a single-intervention group of three measures, a dual-intervention group, and a blank control group. After the intervention, tumor-growth curve method, tumor-inhibition rate method, and bioluminescence method were used to detect the tumor treatment effect. ELISA was used to detect CXCL9 and IL-7 molecule concentration in the serum and tissue homogenate of animals in each group. Results The therapeutic results of animal models showed that the tumor growth in the triple-intervention group of recombinant oncolytic poxvirus+CTL+immune checkpoint blocker (PD-1 monoclonal antibody) was significantly slower than those in the other intervention and the blank control group. Conclusion The combination of recombinant oncolytic poxvirus intratumoral injection+CTL+immune checkpoint blocker (PD-1 monoclonal antibody) exert a strong antitumor effect in intervention experiments on gastric-cancer animal models.
Résumé
Objective @#Objective @*Methods @#The expression levels of PATL1 in pancar- cinoma，gastric cancer and normal tissues were analyzed by TCGA database．The expression level of PATL1 in 40 human gastric cancer tissues and paired adjacent tissues was evaluated by quantitative real-time PCR (RT-qPCR) . The Kaplan-Meier Plotter database was used to analyze the prognosis of PATL1 in gastric cancer patients．The gas- tric cancer cell line AGS was transfected with PATL1 interference vector，and the interference effect was evaluated by RT-qPCR. The effects of PATL1 on the proliferation and migration of AGS were detected by cell counting kit-8 ( CCK-8) ，Transwell test and scratch healing test．The effects of interference with PATL1 on the expression of cel- lular-myelocytomatosis viral oncogene ( c-Myc) and autophagy related 7 ( ATG7) proteins in gastric cancer cells were detected by Western blot assay. @*Results @#RT-qPCR showed that the expression of PATL1 in human gastric cancer tissue was higher than that in normal gastric tissue (P＜0. 001) ，and PATL1 was correlated with the progno- sis of patients with enteric gastric cancer (P＜0. 000 1) ．After PATL1 was knocked down，the number of prolifera- ting and migrating gastric cancer cells decreased (P＜0. 05) ．Western blot test results showed that the expression level of ATG7 protein decreased after PATL1 was knocked down (P＜0. 05) ．@*Conclusion @#PATL1 may inhibit the proliferation and migration of gastric cancer cells through crosstalk with c-Myc and ATG7 .
Résumé
ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.
Résumé
Objective @#To investigate the associations of the single nucleotide polymorphism ( SNP) rs2304733 in TEA domain transcription factor 1 ( TEAD1) , rs7135838 and rs1990330 in TEA domain transcription factor 4 (TEAD4) genes with the risk of non⁃cardia gastric carcinogenesis . @*Methods @#Enzyme linked immunosorbent assay ( ELISA) was used to detect specific antibodies against Helicobacter pylori(Hp)in serum samples of the normal control group . 470 normal controls were divided into Hp infection negative group (n = 223) and positive group ( n = 247) based on antibody titers . In the 450 non⁃cardia gastric cancer cases and 470 controls , polymerase chain reaction⁃restriction fragment length polymorphism (PCR⁃RFLP) was used to genotype the each SNP locus . The unconditional Logistic regression method was used to evaluate the associations between each SNP locus and the risk of non⁃cardia gastric carcinogenesis .@*Results @#The SNPs of TEAD1 and TEAD4 were not associated with Hp infection . TEAD1 rs2304733 was associated with the risk of non⁃cardia gastric cancer. Compared with the carriers of TT genotype , the carries of CT and CC genotypes had an increased risk of non⁃cardia gastric cancer (CT vs TT : OR = 2. 321 , 95% CI : 1 . 690 - 3 . 188 ; CC vs TT : OR = 5 . 140 , 95% CI : 1 . 080 - 24. 463) . TEAD4 rs1990330 was associated with the risk of non⁃cardia gastric cancer. Compared with the carriers of GG genotype , those with GT genotype had an increased risk of non⁃cardia gastric cancer ( OR = 2. 405 , 95% CI : 1 . 480 - 3 . 908 ) . TEAD4 rs7135838 was not associated with the risk of non⁃cardia gastric cancer. TEAD1 rs2304733 , TEAD4 rs7135838 and rs1990330 had interaction effects on the risk of non⁃cardia gastric cancer (P < 0. 05) . @*Conclusion @#In Baotou Han population , TEAD1 rs2304733 and TEAD4 rs1990330 do not play a major role in Hp infection , but may play a role in the risk of non⁃cardia gastric cancer. TEAD4 rs7135838 may not play a major role in the risk of Hp infection and non⁃cardia gastric cancer. TEAD1 rs2304733 and TEAD4 rs1990330 have the strongest synergistic effect on the risk of non⁃cardia gastric cancer , which is the best interaction model .
Résumé
Objective To investigate the expression of LncRNA HOXA-AS2 in gastric cancer tissues and its effect on the malig-nant biology of gastric cancer.Methods The expression levels of lncRNA HOXA-AS2 in gastric cancer tissues and gastric cancer cell lines were detected by qPCR;the effect of lncRNA HOXA-AS2 on the prognosis of gastric cancer patients was analyzed by Kaplan-Meier Plotter,an online website for bioinformatics analysis;the correlation between the expression levels of lncRNA HOXA-AS2 and the clinical and pathological characteristics of gastric cancer patients;cell lines interfering with the expression of lncRNA HOXA-AS2 were constructed,and the effects of down-regulation of lncRNA HOXA-AS2 on the proliferation ability,migration ability and invasion ability of gastric cancer cells were analyzed using CCK8,clone formation assay,scratch assay and Transwell assay.Results The expression lev-el of lncRNA HOXA-AS2 was significantly upregulated in gastric cancer tissues compared with paraneoplastic tissues;the expression lev-el of lncRNA HOXA-AS2 was significantly higher in gastric cancer cell lines compared with human normal gastric mucosal cells GES(P＜0.05);survival analysis showed that high expression of lncRNA HOXA-AS2 was associated with poor prognosis of gastric cancer patients;lncRNA HOXA-AS2 expression level correlated with gastric cancer stage,lymph node metastasis and differentiation(P＜0.05);the expression level of lncRNA HOXA-AS2 was significantly decreased in gastric cancer cells transfected with SiRNA(P＜0.05),and their cell proliferation,migration,and invasion ability were also significantly decreased(P＜0.05).Conclusion lncRNA HOXA-AS2 plays an oncogene role in gastric cancer and is associated with prognosis.Down-regulation of lncRNA HOXA-AS2 ex-pression can inhibit the proliferation,migration,and invasion ability of gastric cancer cells.
Résumé
Patients with gastric cancer are at high risk for venous thromboembolism(VTE)and bleeding,and patients who develop VTE are often associated with poor outcomes,making it clinically challenging to identify and manage the risk of thrombosis in patients with gastric cancer.Risk factors for VTE in gastric cancer patients include age,obesity,surgery,chemotherapy,etc.It is essential to identify high-risk patients and adopt aggressive prevention strategies.The main strategy to prevent and treat VTE is the use of anticoagulant drugs.This article discusses guidelines and recent studies for the prevention and treatment of VTE in patients with gastric cancer to help clinicians make individualized decisions for their patients and maximize clinical outcomes for their patients.
Résumé
Gastric cancer,a malignant tumor with high morbidity and mortality in China,has characteristics such as high heterogeneity and poor prognosis.With the advent of the 21st century,significant progress has been made in gastric cancer diagnosis and treatment due to the rapid development of genomics,laparoscopic minimally invasive techniques,targeted therapy and immunotherapy.This article summarized the important research progress in the field of gastric cancer prevention and treatment since the 21st century,and looked forward to the future.We hope to make greater progress and breakthroughs in early screening,diagnosis and precise treatment of gastric cancer,further improve the overall survival rate of patients,and transform gastric cancer into a controllable"chronic disease".
Résumé
Gastric cancer poses a serious threat to the health of people.Despite the continuous breakthroughs in the development of new drugs such as chemotherapy,targeted therapy and immunotherapy in recent years,radical surgery remains the cornerstone in the treatment of gastric cancer.With the establishment of standard gastric cancer surgery,the advancement of minimally invasive surgical techniques represented by laparoscopy,the determination of perioperative comprehensive treatment of advanced gastric cancer and the formation and initial practice of precise surgical concepts for gastric cancer,the progress of surgical treatment for gastric cancer is advancing by leaps and bounds.The concepts of individualized and optimal treatment are gradually taking root.Safety,effectiveness,precision and minimally invasive approaches have always been the inherent laws of discipline development firmly grasped by gastric cancer surgeons.In order to facilitate better growth for young doctors,the author summarized the latest developments in the diagnosis and treatment of gastric cancer and looked ahead to future trend.
Résumé
Gastric cancer is one of the common malignant tumors of digestive system in our country.The proportion of patients in advanced and late stage is large,and the choice of perioperative treatment program is always difficult in clinic.For most locally advanced gastric cancer,compared with standard radical surgery combined with postoperative adjuvant chemotherapy,perioperative treatment mode may further improve the survival of patients.However,the efficacy of conventional chemotherapy regimen has reached a plateau,while the progress of traditional molecular targeted therapy is relatively slow.In recent years,with the increasing role of immunotherapy in the treatment of advanced gastric cancer,more and more clinical studies have shown that immunotherapy can also achieve better efficacy in perioperative gastric cancer patients.This article reviewed the research progress of immunotherapy in perioperative gastric cancer in recent years.
Résumé
Background and purpose:Follow-up data of 6 737 patients undergoing surgery for gastric cancer were collected based on hospital registration,and the 1-,3-and 5-years observed overall survival(OS)rates and disease-free survival(DFS)rates were analyzed to provide real-world research evidence for the prevention and control of gastric cancer and policy making in China.Methods:A total of 6 737 gastric cancer patients who underwent surgical treatment at Fudan University Shanghai Cancer center from 2015 to 2020 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was November 30,2023.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year OS rate and DFS rate,and survival data were described by different subgroups including age group,gender,treatment period,tumor staging,and pathological characteristics.Results:With a median follow-up time of 50.99 months,the 5-year OS rate of surgically resected gastric cancer patients was 70.37%,and 5-year DFS rate in Ⅰ-Ⅲ stage cases was 69.46%.The 5-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 94.32%,82.56%,51.01%and 23.97%,respectively.The differences in survival among patients with different age,tumor location,gross classification,Borrmann classification and Laurence classification were significant.Conclusion:Staging is an important factor directly affecting the survival of gastric cancer patients.Screening and early diagnosis and treatment in large population,especially high-risk group,should be strengthened to further improve the patients'survival.
Résumé
Background and purpose:Trastuzumab has a relatively low incidence of drug resistance,which can be used as an adjuvant treatment to improve clinical efficacy.It has been used to treat breast cancer in the past,but its application in other cancers has been less studied.This study aimed to explore the effects of trastuzumab assisted modified DOF fortnightly regimen on serum tumor markers and survival rate in cisplatin-resistant gastric cancer patients,in order to provide more references for the selection of clinical treatment methods for cisplatin-resistant gastric cancer.Methods:Eighty patients with cisplatin-resistant gastric cancer treated in Harison International Peace Hospital from January 2017 to January 2019 were selected as the study objects,and they were divided into observation group and control group according to random number table method.All of them received improved DOF fortnightly treatment,and trastuzumab adjuvant treatment was added to the observation group on this basis.The serum tumor markers[serum carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),CA72-4],serum neovascular markers[vascular endothelial growth factor(VEGF),pigment epithelial derived factor(PEDF),angiopoietin-2(Ang-2)],biochemical indicators[N-terminal pro B type natriuretic peptide(NT proBNP),aspartate transaminase(AST),blood urea nitrogen(BUN),alanine aminotransferase(ALT)],adverse reactions and survival rate were compared between two groups.This study was approved by the Ethics Committee of Harison International Peace Hospital(number:20160511).Results:After treatment,CEA,CA19-9 and CA72-4 in both groups decreased,and CEA,CA19-9 and CA72-4 levels were lower in the observation group than in the control group with statistical significance(P＜0.01).After treatment,VEGF,PEDF and Ang-2 in two groups decreased,and the difference was statistically significant(P＜0.01).The levels of VEGF,PEDF and Ang-2 were compared between the two groups before and after treatment,and there was no significant difference(P＞0.05).The levels of NT-proBNP,AST,BUN and ALT were compared between the two groups before and after treatment,and there was no statistically significant difference(P＞0.05).The number of patients with fatigue,gastrointestinal reaction and myelosuppression and the total incidence of adverse reactions were compared between the two groups,and there was no statistically significant difference(P＞0.05).At 5 years after treatment,11 cases(27.5%)survived and 29 cases(72.5%)died in the observation group.There were 3 cases(7.5%)of survival and 37 cases(92.5%)of death in the control group.The median survival was 2 years(95%CI:1.8-2.2)in the observation group and 1 year(95%CI:0.6-1.4)in the control group.The survival rate of 1-5 years was higher in the observation group than in the control group.The difference was statistically significant(log-rank χ2 = 13.853,P = 0.001).Conclusion:In the clinical treatment of cisplatin-resistant gastric cancer,trastuzumab assisted modified DOF fortnightly regimen suggests that it can reduce the expression levels of serum tumor markers,improve the 5-year survival rate of patients,and has certain drug safety.
Résumé
AIM:To observe the effect of Pingwei capsule on the precancerous lesions of gastric cancer(PLGC)cell model induced by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG),and to preliminarily explore its mecha-nism.METHODS:Blank serum and Pingwei capsule-containing serum were prepared for later use.A PLGC cell model was established by MNNG-induced human gastric mucosal epithelial cell line GES-1.To evaluate the model,cell morpho-logical changes were observed under inverted microscope,and the expression of proliferating cell-related antigen Ki67 was detected by immunofluorescence staining.CCK-8 assay was used to screen the optimal intervention concentration and time of serum containing drugs.Reactive oxygen species(ROS)content in cells was detected using a fluorescent probe DCFH-DA.Malondialdehyde(MDA)content was detected by ELISA,and the activity of superoxide dismutase(SOD)and gluta-thione peroxidase(GSH-Px)was detected using biochemical reagents.A novel fluorescent probe JC-10 was used to detect mitochondrial membrane potential.The mRNA expression levels of Ki67 and melanoma differentiation-associated gene-7(MDA-7)were detected by real-time fluorescence quantitative PCR.The protein expression levels of Ki67,interleukin-6(IL-6)and MDA-7 were detected by Western blot.RESULTS:Compared with normal group,the ROS and MDA levels in model group and blank serum group were significantly increased(P<0.01),while the activity of SOD and GSH-Px was significantly decreased(P<0.01).The mitochondrial membrane potential was significantly decreased(P<0.01).The protein expression levels of Ki67 and IL-6 were significantly increased(P<0.01),while the protein expression level of MDA-7 was significantly decreased(P<0.01).There were no significant differences of the above indicators between model group and blank serum group(P>0.05).Compared with blank serum group,the Pingwei capsule-containing serum group showed significantly decreased ROS and MDA levels(P<0.01),significantly increased activity of SOD and GSH-Px(P<0.05),significantly increased mitochondrial membrane potential(P<0.01),significantly decreased protein expres-sion levels of Ki67 and IL-6(P<0.01),and significantly increased protein and mRNA expression levels of MDA-7(P<0.01).CONCLUSION:Pingwei capsule can significantly alleviate MNNG-induced oxidative damage and inflammatory response,and regulate the expression of oncogenes and tumor suppressor genes,thereby playing a role in prevention and treatment of PLGC.
Résumé
AIM:To investigate the effect of doublecortin-like kinase 1(DCLK1)on the biological properties of gastric cancer stem cells,and to explore its possible mechanism.METHODS:Serum-free suspension culture of gastric cancer stem cells and targeted inhibition of DCLK1 activity in gastric cancer stem cells with DCLK1 inhibitor DCLK1-IN-1 were performed.The expression levels of DCLK1,stemness-related proteins(SOX2 and OCT4),proliferation-related pro-teins(cyclin D1 and c-MYC),drug resistance-related proteins(ABCG2 and TOP2A),epithelial-mesenchymal transition-related proteins(E-cadherin,vimentin and Snail),and PI3K/AKT/mTOR signaling pathway-related proteins in gastric cancer stem cells were examined by Western blot.The effects of DCLK1 on viability and drug resistance of gastric cancer stem cells were determined by CCK-8 assay,and the effects of DCLK1 on self-renewal of gastric cancer stem cells were de-termined by methylcellulose spheroid-forming assay.Wound-healing and Transwell assays were performed to assess the ef-fect of DCLK1 on the migration and invasion of gastric cancer stem cells.RESULTS:The expression levels of DCLK1 and stemness-related proteins SOX2 and OCT4 in gastric cancer stem cells were significantly higher than those in parental cells(P＜0.01).The proliferation,drug resistance,migration and invasion of gastric cancer stem cells in DCLK1 inhibi-tion group were significantly lower than those in Sphere cell group(P＜0.01).The expression levels of proliferation-related proteins(c-MYC and cyclin D1)and drug resistance-related proteins(TOP2A and ABCG2)were down-regulated,the ex-pression of epithelial marker E-cadherin was up-regulated,the expression of mesenchymal markers vimentin and Snail was down-regulated,and the expression levels of PI3K/AKT/mTOR signaling pathway-related proteins and their phosphoryla-tion levels were reduced in DCLK1 inhibition group(P＜0.05).CONCLUSION:DCLK1 is highly expressed in gastric cancer stem cells,which may be involved in the proliferation,drug resistance and invasion of gastric cancer stem cells by regulating PI3K/AKT/mTOR signaling pathway.It suggests that DCLK1 can be used as a potential target for gastric cancer stem cells.